BackgroundHand-foot syndrome (HFS) is one of the most common toxicities experienced by patients receiving systemic chemotherapy agents such as capecitabine and multikinase inhibitors such as sorafenib. Several randomised controlled trials (RCTs) have investigated the efficacy and safety of prophylactic agents such as pyridoxine, celecoxib, urea cream and cystine/theanine in managing HFS. This network meta-analysis (NMA) evaluated data from high-quality trials to provide strong evidence in forming recommendations to prevent systemic cancer therapy-induced HFS.ObjectiveTo examine the comparative efficacy and safety of interventions for preventing systemic chemotherapy-induced HFS in patients with cancer.MethodsWe searched PubMed, Embase and clinical trial registry for RCTs of interventions for preventing HFS. Bayesian NMA was performed to estimate the OR with 95% credible intervals (CrI) from both direct and indirect evidence. The outcome measures were the incidence of HFS (grade ≥1) and moderate to severe HFS (grade ≥2). Adverse drug reactions were discussed descriptively.ResultsA total of 15 RCTs with 2715 patients with 12 prophylactic strategies were included. The analysis showed only celecoxib could significantly prevent the incidence of moderate to severe HFS (grade ≥2) (OR 0.29, 95% CrI 0.13 to 0.68). But none of the preventive interventions could prevent the incidence of HFS (grade ≥1).ConclusionOnly celecoxib (200 mg two times per day) showed significant prevention of the incidence of moderate to severe HFS. Pyridoxine (400 mg once daily) and urea cream (10%) have to be evaluated further in larger randomised trials.